EE-ASI 1

• Register: EUCTR
• Last refreshed on: 13 July 2020
• Main ID: EUCTR2015-003934-28-GB
• Date of registration: 04/12/2015
• Prospective Registration: Yes
• Primary sponsor: Cardiff University
• Public title: EE-ASI 1
• Scientific title: Enhanced Epidermal Antigen Specific Immunotherapy trial -1 (EE-ASI-1): A Phase 1a study of gold nanoparticles administered intradermally by microneedles to deliver immunotherapy with a proinsulin derived peptide in Type 1 diabetes. - EE-ASI-1
• Date of first enrolment: 04/03/2016
• Target sample size: 4
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003934-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Sweden, United Kingdom

Contacts

• Name: Professor Colin Dayan
• Affiliation: Cardiff University

• Name: Professor Colin Dayan
• Affiliation: Cardiff University

Key inclusion & exclusion criteria

Inclusion criteria:
1.Clinical diagnosis of type 1 diabetes for > 3 months (dated from the first insulin injection).
2.Commenced on insulin treatment within 1 month of diagnosis after diagnosis.
3.Age 16 to 40 years
4.2 hour post-meal UCPCR > 0.53 nmol/mmol on at least one occasion (maximum 3 tests on different days)
5.Possession of 0401 allele at the HLA-DRB1 gene locus

If female, must be (as documented in patient notes):
a.surgically sterile (tubal ligation or hysterectomy at least 6 months prior to enrolment), or
b.using acceptable contraception (e.g., oral, intramuscular, or implanted hormonal contraception) at least 3 months prior to enrolment, or
c.have a sexual partner with non-reversed vasectomy (with confirmed azoospermia), or
d.be using 1 barrier method with the use of a spermicide(e.g., condom, diaphragm or cap)
e.have placement of a intra-uterine device
6.If male, must be:
a.using a barrier method of contraception (condom) with the use of a spermicide. or
b. have a sexual partner using one of the methods in point 7 above or
c.have a non-reversed vasectomy (with confirmed azoospermia),
7.Written and witnessed informed consent to participate.

Are the trial subjects under 18? yes
Number of subjects for this age range: 2
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 6
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1.HbA1c > 86mmol/L (10%).
2.Females who are pregnant, breast-feeding or not using adequate forms of contraception.
3.Previous diagnosis of renal disease including glomerulonephritis or nephropathy.
4.Raised serum creatinine or abnormal urine albumin/creatinine ratio (ACR). If the initial ACR is raised, this should be repeated on two further occasions as first morning samples. The subject can be included if both of these samples are negative (within the reference range).
5.Use of immunosuppressive or immunomodulatory therapies, including systemic steroids within 1 month prior to receiving the IMP and any monoclonal antibody therapy given for any indication. Note that previous exposure to proinsulin peptide C19-A3 in a clinical trial is not an exclusion criterion.
6.Use of any hypoglycaemia agents other than insulin, for more than 6 weeks, at any time prior to trial entry.
7.Use of inhaled insulin.
8.Known alcohol abuse, drug abuse, HIV or hepatitis.
9.Any other medical condition which, in the opinion of investigators, could affect the safety of the subject’s participation or outcomes of the study, including immunocompromised states and autoimmune conditionsor outcomes of the study, including immunocompromised states and autoimmune conditions.
10.Subjects should not have had immunisations (flu and others) for 1 month prior to trial entry and should not receive any during their time in the trial
11.Recent subject’s involvement in other research studies which, in the opinion of investigators, may adversely affect the safety of the subjects or the results of the study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Type 1 diabetes
MedDRA version: 18.1 Level: PT Classification code 10067584 Term: Type 1 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders

Intervention(s)

Product Name: C19-A3 GNP intradermal micro-injectable solution of human C19-A3 pro-insulin peptide coupled to gold
Product Code: C19-A3 GNP
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Human C19-A3 proinsulin peptide coupled to gold nanoparticles (GNPs)
CAS Number: N/A
Current Sponsor code: SPON1455-15
Other descriptive name: C19-A3 GNP
Concentration unit: µg/µl microgram(s)/microlitre
Concentration type: equal
Concentration number: 10µg of peptide-

Primary Outcome(s)

Primary end point(s): The primary outcome measure for the trial is the safety (adverse event) profile of this investigational agent.

Secondary Objective: Secondary objectives are:
•To study the feasibility of delivering C19-A3 GNP via microneedles to humans.
•To study the size and nature of immune responses to C19-A3 GNP generated in blood and the draining (axillary) lymph node.

Main Objective: The primary objective of the study is to examine the risk of C19-A3 GNP administration in terms of general safety and induction of hypersensitivity.

Timepoint(s) of evaluation of this end point: The following time points are set for evaluation of adverse event profiles, but pharmacovigilance data will be collected at times points in between if events arise:
2hours
4 weeks
8 weeks
14 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: See point 23.2

Secondary end point(s): Secondary endpoints and timepoints:
•T cell responses to GNP C19-A3 as determined by changes from baseline of interferon gamma and IL-10 ELISPOT responses to this peptide in blood following treatment at weeks 0, 8 and 14.
•T cell responses to GNP C19-A3 as determined by changes from baseline of interferon gamma and IL-10 ELISPOT responses to this peptide in draining axillary lymph node before and after the first and last treatment administration.
•Changes in additional immunological biomarkers (e.g. flow cytoemtry profiles, T reg assays, beta cell and T cell cell free DNA markers) from baseline at week 0, 8 and 14.
•Effects on residual c-peptide secretion at week 12 as compared to baseline as assessed by a mixed meal tolerance test and a stimulated urine c-peptide test.
•Effects on glycaemic control assessed by blood sugar profiles and HbA1c at week 14 as compared to baseline
•Questionnaires on quality of life and diabetes self-management at baseline and week 14.

Secondary ID(s)

SPON1455-15

Source(s) of Monetary Support

European Commission

Ethics review

Status: Approved
Approval date: 04/03/2016
Contact: